We are following a diverse cohort of volunteer women from throughout the US and Puerto Rico between the ages of 35 and 74 who have a sister with breast cancer but did not have breast cancer themselves at enrollment. At enrollment, data on potential risk factors and current health status were collected using computer assisted telephone interviews and mail questionnaires. Blood, urine, and environmental samples were collected in a home visit and banked for future use in nested studies of women who develop breast cancer (or other diseases) and a sample of those who don't. The cohort is tracked annually for changes in vital status and major health outcomes. Detailed follow-up questionnaires are completed every 2-3 years. Medical records and tumor tissue (for breast cancer cases) are retrieved for those who develop cancer or other conditions of interest. The cohort was enrolled between 2003 and 2009. Nearly 51,000 women completed all baseline study activities. The response rates for annual updates range from 90-98%. Biennial follow-up questionnaires have been collected from 44,141 eligible women date. More than 1,500 women have reported a diagnosis of breast cancer or DCIS;medical records and tumor tissue are being sought for those 6 months post diagnosis. Analyses exploring risk factors for breast cancer and other health conditions are ongoing. Using data collected at baseline, we have examined eating patterns and sleep duration, employment and work schedule and telomere length, lifestyle behaviors in black and white women, and early life factors in relation to age at menopause. We also reported on early life factors and fibroids in black women, a companion to our previously reported study of uterine fibroids in whites. Using data from a case-cohort study involving the first 350 breast cancer cases and a sample of 700 women selected from the cohort, we completed an analysis of telomere length in peripheral blood and breast cancer risk, finding no association in our prospectively collected data. Papers in progress include early life exposures and age at menarche as well as in relation to risk for rheumatoid arthritis, accuracy and reliability of self-reported weight and height, and genetic variants and breast cancer risk. Results of several analyses have been presented at national scientific meetings and manuscripts are in preparation for publication. In a new effort, the Sister Study is conducting research related to breast cancer survival in collaboration with researchers from the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention, headed by Dr. Mary White, chief of their Epidemiology and Applied Research Branch. This collaborative undertaking is funded in part through the Young Women's Breast Health Awareness and Support of Young Women Diagnosed with Breast Cancer bill, a 2010 congressional bill also known as the EARLY Act. As part of this effort, in January 2011, the Sister Study held a workshop on state-of-the-art research on breast cancer survivors. Experts from across the United States discussed four general topic areas: behavioral, psychosocial, and economic outcomes, health effects after treatment, reproductive health after treatment and cancer recurrence and long-term cancer-free survival. The workshop resulted in recommendations on how the Sister Study can best contribute to these areas of research. We have also developed a special questionnaire for the annual follow-up this year that covered breast cancer screening and the effect having a sister with breast cancer has had on Sister Study participants and their families. We are in the planning stages for a special survey of breast cancer survivors that will focus on quality of life and other concerns for women who have experienced a breast cancer diagnosis and treatment. Data collection for a small validation study of self-reported early life factors was completed this year. The aim of the study was to evaluate how accurately women reported the information on early life collected at baseline, including information on their mother's pregnancy. A total of 1,802 mothers completed a questionnaire after receiving an invitation from their daughter. Data analysis is ongoing and involves comparing mothers and daughters responses. Preliminary results suggest moderate or better agreement for most of the factors studied. In conjunction with a co-investigator at the University of Washington, geocoding of Sister Study addresses is nearly finished. Geocoding allows us to obtain U.S. Census neighborhood-level information and data on environmental exposures such as current and historical air pollution near participant residences. Progress has been made on a small study of the determinants of urinary prostaglandin E2-metabolite (PGE-M) and the interaction between urinary PGE-M levels and estrogen biosynthesis in relation to breast cancer risk in 609 (301 cases and 308 subcohort members) postmenopausal women. Measurement of urinary PGE-M and creatinine is nearly completed. Data from half of the study samples were used in preliminary data analyses and results presented at the 2011 Era of Hope Meeting at Orlando, Florida. Current work focuses on improving the assay for urinary estrogen measurements. Enrollment has been completed for a related study known as the Two Sister Study that builds on the Sister Study by recruiting the Sister Study participant's sister with breast cancer as well as parents who are asked to provide a saliva sample to be used as a source of DNA for family-based analyses of genetic factors associated with breast cancer risk. Eligible affected sisters were diagnosed before the age of 50 and within 3 years of her sisters enrollment in the Sister Study. Over 1,300 affected sisters completed all baseline activities and over 1,300 of their parents provided saliva samples. Data analysis is ongoing with the first analyses examining infertility drug and hormone use in relation to breast cancer risk.